Claims for Patent: 10,238,634
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Summary for Patent: 10,238,634
| Title: | Aqueous-based metronidazole gel formulations |
| Abstract: | The present disclosure provides mucoadhesive aqueous-based gel formulations of metronidazole useful for a variety of purposes, including intravaginal application as a therapeutic approach towards the treatment of individuals suffering from and/or diagnosed with bacterial vaginosis. |
| Inventor(s): | Nordsiek; Michael T. (Wayne, PA), Balaji; Kodumudi S. (Landsdale, PA) |
| Assignee: | CHEMO RESEARCH, S.L. (Madrid, ES) |
| Application Number: | 14/921,737 |
| Patent Claims: |
1. An intravaginal aqueous based gel composition comprising: a) metronidazole in a concentration of about 1.3% to about 1.5% by weight of the aqueous based gel composition;
b) about 1% to about 3% by weight of the aqueous based gel composition of one or more mucoadhesive gelling polymers; c) about 30% to about 60% of water by weight of the aqueous based gel composition; and d) a ternary solvent system in a concentration
of about 30% to about 60% by weight of the aqueous based gel composition, wherein the ternary solvent system comprises: i) one or more lower aromatic alcohols selected from the group consisting of benzyl alcohol, 2-methylbenzyl alcohol, phenoxyethanol,
and mixtures thereof; ii) one or more lower alkylene diols selected from the group consisting of ethane-1,2-diol (ethylene glycol), propane-1,2-diol (propylene glycol), and mixtures thereof; and iii) one or more polyoxyalkylenes selected from the group
consisting of polyoxyethylene (polyethylene glycol), polyoxypropylene, (polypropylene glycol) and mixtures thereof; said aqueous based gel composition exhibiting a viscosity ranging from about 200,000 mPas to about 400,000 mPas, measured at 25.degree.
C. using the controlled shear rate method, a Bohlin CVO 100 rheometer and the rheometer settings of Table 11 and having an aqueous phase with a pH ranging from about 3.0 to about 5.0.
2. The gel composition of claim 1 wherein the one or more mucoadhesive gelling polymers are selected from the group consisting of hydroxyethylcellulose, a carbomer, a polycarbophil, and mixtures thereof. 3. A method of treating a subject with bacterial vaginosis, comprising applying intravaginally to the subject a single administration of the aqueous-based gel composition of claim 1. 4. A method of treating a subject with bacterial vaginosis, comprising administering intravaginally to the subject a single dose aqueous based metronidazole gel composition wherein the single dose aqueous based metronidazole gel composition is administered once a day for one, two or three days, and the single dose aqueous based metronidazole gel composition comprises: i) 60-70 mg of metronidazole in a concentration of about 1.3% to about 1.5% by weight of the aqueous based metronidazole gel composition; ii) about 30% to about 60% of water by weight of the single dose aqueous based metronidazole gel composition; iii) about 1% to about 3% by weight of the single dose aqueous based metronidazole gel composition of at least one mucoadhesive gelling polymer; and iv) about 30% to about 60% of a ternary solvent system by weight of the single dose aqueous based metronidazole gel composition, the ternary solvent system comprising: 1) one or more lower aromatic alcohols selected from the group consisting of benzyl alcohol, 2-methylbenzyl alcohol, phenoxyethanol, and mixtures thereof; 2) one or more lower alkylene diols selected from the group consisting of ethane-1,2-diol (ethylene glycol), propane-1,2-diol (propylene glycol), and mixtures thereof; and 3) one or more polyoxyalkylenes selected from the group consisting of polyoxyethylene (polyethylene glycol), polyoxypropylene, (polypropylene glycol) and mixtures thereof; wherein the single dose aqueous based metronidazole gel exhibits: a) a pH ranging from about 3.0 to about 5.0; and b) a viscosity of about 200,000 mPas to about 400,000 mPas at 25.degree. C. using a controlled shear rate ramp method, a Bohlin CVO 100 rheometer and the rheometer settings of Table 11. 5. The method of claim 4 wherein the one or more mucoadhesive gelling polymers are selected from the group consisting of hydroxyethylcellulose, a carbomer, a polycarbophil, and mixtures thereof. 6. The intravaginal aqueous based gel composition of claim 1 wherein the one or more lower aromatic alcohols comprises about 1% to about 5% of weight of the ternary solvent system. 7. The method of claim 4 wherein the one or more lower aromatic alcohols comprises about 1% to about 5% by weight of the ternary solvent system. 8. An intravaginal aqueous based gel composition comprising: a) metronidazole in a concentration of about 1.3% to about 1.5% by weight of the aqueous based gel composition; b) about 1% to about 3% by weight of the aqueous based gel composition of one or more mucoadhesive gelling polymers selected from the group consisting of hydroxyethylcellulose, a polycarbophil, and mixtures thereof; c) about 30% to about 60% of water by weight of the aqueous based gel composition; and d) a ternary solvent system in a concentration of about 30% to about 60% by weight of the aqueous based gel composition, wherein the ternary solvent system consists of: i) about 1.3% to about 2.5% by weight of the aqueous based gel composition of one or more lower aromatic alcohols selected from the group consisting of benzyl alcohol, 2-methylbenzyl alcohol, phenoxyethanol, and mixtures thereof; ii) about 3% to about 20% by weight of the aqueous based gel composition of one or more lower alkylene diols selected from the group consisting of ethane-1,2-diol (ethylene glycol), propane-1,2-diol (propylene glycol), and mixtures thereof; and iii) about 10% to about 50% by weight of the aqueous based gel composition of one or more polyoxyalkylenes selected from the group consisting of polyoxyethylene (polyethylene glycol), polyoxypropylene, (polypropylene glycol) and mixtures thereof; said aqueous based gel composition exhibiting a viscosity ranging from about 200,000 mPas to about 400,000 mPas, measured at 25.degree. C. using a controlled shear rate method, a Bohlin CVO 100 rheometer and the rheometer settings of Table 11 and having an aqueous phase with a pH ranging from about 3.0 to about 5.0. 9. The intravaginal aqueous based gel composition of claim 8 wherein the one or more mucoadhesive gelling polymers is a polycarbophil and the ternary solvent system consists of: i) about 1.3% to about 2.5% by weight of the aqueous based gel composition of benzyl alcohol; ii) about 3% to about 20% by weight of the aqueous based gel composition of propylene glycol; and iii) about 10% to about 50% by weight of the aqueous based gel composition of polyethylene glycol. |
